Leucine Aminopeptidase-Mediated Multifunctional Molecular Imaging Tool for Diagnosis, Drug Evaluation, and Surgical Guidance of Liver-Related Diseases,Analytical Chemistry

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Leucine Aminopeptidase-Mediated Multifunctional Molecular Imaging Tool for Diagnosis, Drug Evaluation, and Surgical Guidance of Liver-Related Diseases
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-07-31 , DOI: 10.1021/acs.analchem.3c02130
Lanlan Xu ₁ , Mo Ma _{1,

2} , Jingkang Li ₁ , Dejiang Gao ₁ , Pinyi Ma ₁ , Fangmei Zhang ₃ , Daqian Song ₁

Affiliation

Traditional molecular imaging tools used for detecting liver diseases own several drawbacks, such as poor optical performance and limited applicability. Monitoring the concentration of leucine aminopeptidase (LAP), which is closely related to liver diseases such as liver cancer and liver injury, and analyzing it in diagnosis, drug evaluation, and surgical treatment is still a challenging task. Herein, we construct an intramolecular charge-transfer mechanism-based, ultrasensitive, near-infrared fluorescent probe (LAN-lap) for dynamic monitoring of LAP fluctuations in living systems. LAN-lap, with high specificity, stability, sensitivity, and water solubility, can achieve in vitro monitoring of LAP through both fluorescence and colorimetric methods. Moreover, LAN-lap can successfully be used for the localization imaging of endogenous LAP, confirming the upregulation of LAP expression in liver cancer and liver injury cells. In addition, LAN-lap can realize the imaging of liver tumors in living organisms. Meanwhile, it can intuitively present the degree of drug-induced liver injury, achieving semi-quantitative imaging evaluation of the hepatotoxicity of two drugs. Furthermore, LAN-lap can track liver cancer tumors in mice with peritoneal metastasis and can assist in fluorescence-guided surgical resection of liver cancer tumors. This multifunctional LAN-lap probe could play an important role in facilitating simultaneous diagnoses, imaging, and synergistic surgical navigation to achieve better point-of-care therapeutic efficacy.

中文翻译：

亮氨酸氨肽酶介导的多功能分子影像工具，用于肝脏相关疾病的诊断、药物评价和手术指导

用于检测肝脏疾病的传统分子成像工具存在光学性能差、适用性有限等缺点。亮氨酸氨基肽酶（LAP）的浓度与肝癌和肝损伤等肝脏疾病密切相关，监测其浓度并在诊断、药物评价和手术治疗中进行分析仍然是一项具有挑战性的任务。在此，我们构建了一种基于分子内电荷转移机制的超灵敏近红外荧光探针（LAN-lap），用于动态监测生命系统中的 LAP 波动。LAN-lap具有较高的特异性、稳定性、灵敏度和水溶性，可以通过荧光和比色方法实现LAP的体外监测。此外，LAN-lap可成功用于内源性LAP的定位成像，证实了肝癌和肝损伤细胞中LAP表达的上调。此外，LAN-lap还可以实现活体肝脏肿瘤的成像。同时，可以直观地呈现药物引起的肝损伤程度，实现两种药物肝毒性的半定量成像评价。此外，LAN-lap可以追踪腹膜转移小鼠的肝癌肿瘤，并可以协助荧光引导的肝癌肿瘤手术切除。这种多功能 LAN-lap 探头可以在促进同步诊断、成像和协同手术导航以实现更好的床旁治疗效果方面发挥重要作用。

更新日期：2023-07-31

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